Policosanol is a complex mixture of concentrated long chain N-alkyl alcohols derived from plant sources, such as sugar cane. Octacosanol is a major constituent of naturally derived policosanol, e.g. from sugarcane. Much of the published work on policosanol has been directed to mixtures in which octacosanol was a major component. Early work in Cuba studying the effects of policosanol on serum lipid and lipoprotein levels in healthy volunteers indicated that, at dosages of 2-40 mg/d, policosanol administration reduced serum lipid and lipoprotein levels (Hernandez et al., Curr. Ther. Res. Clin. Exp. 1992; 51: 568), and reduced hypercholesterolemia (Pons et al., Curr. Ther. Res. Clin. Exp.; 1992; 52: 507). However, despite numerous subsequent studies, researchers outside Cuba have been unable to verify the claims made in conjunction with the original research. The ineffectiveness of policosanol on serum lipid/cholesterol levels has been comprehensively documented in respected, peer-reviewed journals.
For example, Francini-Pesenti and coworkers conducted double blinded, randomized, placebo-controlled trials of policosanol in subjects with hypercholesterolemia and concluded that doses of 10 mg/d and 20 mg/d of policosanol showed no lipid lowering effects (Complement Ther. Med.; 2008; 16(2): 61; and Phytother. Res.; 2008; 22(3): 318). In a similar blind, placebo-controlled study, Berthold and coworkers showed that doses of 10, 20, 40 and 80 mg/d of policosanol did not result in lower serum lipid levels than those seen in subjects to whom the placebo was administered (JAMA; 2006; 295(19): 2262). Dullens et al. found that neither individual policosanol components (C24, C26, C28, or C30) nor the natural policosanol mixture (all components, 30 mg/100 g diet) lowered serum cholesterol concentrations in LDL receptor knockout mice (J. Lipid Res.; 2008; 49(4): 790). Kassis and coworkers studied the efficacy of Cuban sugar cane policosanols for treating hypercholesterolemia in humans at a dosage of 10 mg/d and concluded that policosanol had no beneficial effects on lipid indicators in hypercholesterolemia subjects (Am. J. Clin. Nutr; 2006; 84(5): 1003). Lin and coworkers studied the effects of 20 mg/d dosages of wheat germ policosanol in subjects with normal to mildly elevated plasma cholesterol and detected no lowering of plasma cholesterol (Metabolism; 2004; 53(10): 1309). Lukashevich et al. found that beeswax policosanol (10 mg or 40 mg) administered daily in tablet or soft gel formulations had no effect on serum lipids in subjects with mild-to-moderate hypercholesterolemia. (Circulation; 2006; 114: 892). Murphy et al. found dietary supplementation of rabbits with policosanol from sunflower oil did not have any cholesterol lowering effect. (J. Am. College Nutr; 2008; 27(4): 476).
Thus, despite the early apparently promising results of the Cuban research, the conclusion that must be reached from contemporary blinded, placebo-controlled studies is that art-recognized policosanol formulations are not effective at modulating serum lipid/cholesterol levels.
Research on the utility of policosanol formulations on other metabolic and physiologic parameters has produced similarly negative results. For example, policosanol was shown to have no effect on blood sugar levels, glycemic control (Crespo et al., Int. J. Clin. Pharm. Res.; 1999: 117) or diabetic status (Shinbori et al., Eur. J. Pharmacol; 2007; 139-144).
A controversy existed for a time regarding whether the composition or formulation of the policosanol used in the Cuban studies was responsible for the inconsistent results between the Cuban research and that of other workers. This controversy has been put to rest in seminal research. (Kassis, British Journal of Nutrition (2007), 97, 381-388; Kassis, Lipids Health Dis. (2008); 7:17; Kassis Appl. Physiol. Nutr. Metab; (2008); 33(3): 540 and Dullens J. Lipid Res. (2008), 49: 790). They studied utilized different sugar cane derived policosanol formulations, including the formulation used in the Cuban research. Their studies concluded that none of the tested policosanol formulations significantly improved lipid parameters in humans or animals relative to the control. Moreover, the in vivo assessment of LDL oxidation showed no significant alteration in oxidized LDL concentration relative to the baseline and control. Thus, as of mid-2008, the controversy regarding the serum lipid lowering effects of the Cuban as well as other sugar cane policosanol formulations is resolved outside Cuba.
There are very few reports in the literature on the therapeutic effects of pure octacosanol. Kim et. al., (Journal of Medicinal Food. (December 2003), 6(4): 345-351) evaluated the effects of octacosanol on running performance and related biochemical parameters in exercise-trained rats run to exhaustion on a treadmill. Their results suggest that the ergogenic properties of octacosanol include the sparing of muscle glycogen stores and increasing the oxidative capacity in the muscle of exercise-trained rats. Ping-ping Zuo et. al., (Acta Pharmacologica Sinica (July 2010) 31, 765-774) on their rat studies suggested that octacosanol may be a promising agent for treatment of Parkinson's disease. Fallat R J, et. al., (Neurology 1986; 36:1263-1264) found that administration of octacosanol in patients with amyotrophic lateral sclerosis in a double-blind, placebo-controlled, crossover study did not show any benefits to neurologic and pulmonary function. In Jahreis G. (Lipids 2008; 43 (2): 109-15), octacosanol administration to humans decreases neutral sterol and bile acid concentration in feces but serum cholesterol levels were not influenced. S. Kato, et. al., (British Journal of Nutrition (1995), 73:433-441) fed a high-fat diet rats with octacosanol at very high dose of 10 gm/kilo and found that lipid absorption was not affected by the inclusion of octacosanol. Thippeswamy (Eur J Pharmacol 2008; 588 (2-3): 141-50) found that octacosanol inhibits angiogenesis. It is known that angiogenesis is involved in tumor growth and metastasis. Plat et. al (Journal of Lipid Research, Vol. 49, 790-796, April 2008) studied emulsified and finely dispersed policosanol constituents individually and came to the conclusion that the evaluated individual policosanols as well as the natural policosanol mixtures have no potential in reducing CHD risk through effects on serum lipoprotein concentrations.